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INVESTOR DECK INVESTOR DECK INVESTOR DECK SEEKING GENE THERAPY CURES November 2025
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2 DISCLAIMER Various statements in this presentation concerning Rocket’s future expectations, plans and prospects that involve risks and uncertainties, as well as assumptions that, if they do not materialize or prove incorrect, could cause our results to differ materially from those expressed or implied by such forward-looking statements. We make such forward- looking statements pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. All statements other than statements of historical facts contained in this release are forward-looking statements. You should not place reliance on these forward-looking statements, which often include words such as "believe," "expect," "anticipate," "intend," "plan," "will give," "estimate," "seek," "will," "may," "suggest" or similar terms, variations of such terms or the negative of those terms. These forward-looking statements include, but are not limited to, statements concerning Rocket’s expectations regarding the safety and effectiveness of product candidates that Rocket is developing to treat Fanconi Anemia (FA), Leukocyte Adhesion Deficiency-I (LAD-I), Pyruvate Kinase Deficiency (PKD), Danon Disease (DD) and other diseases, the expected timing and data readouts of Rocket’s ongoing and planned clinical trials, the expected timing and outcome of Rocket’s regulatory interactions and planned submissions, Rocket’s plans for the advancement of its DD program, including its planned pivotal trial, and the safety, effectiveness and timing of related pre- clinical studies and clinical trials, Rocket’s ability to establish key collaborations and vendor relationships for its product candidates, Rocket’s ability to develop sales and marketing capabilities or enter into agreements with third parties to sell and market its product candidates and Rocket’s ability to expand its pipeline to target additional indications that are compatible with its gene therapy technologies. Although Rocket believes that the expectations reflected in the forward-looking statements are reasonable, Rocket cannot guarantee such outcomes. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, Rocket’s dependence on third parties for development, manufacture, marketing, sales and distribution of product candidates, the outcome of litigation, unexpected expenditures, Rocket’s competitors’ activities, including decisions as to the timing of competing product launches, pricing and discounting, Rocket’s ability to develop, acquire and advance product candidates into, enroll a sufficient number of patients into, and successfully complete, clinical studies, Rocket’s ability to acquire additional businesses, form strategic alliances or create joint ventures and its ability to realize the benefit of such acquisitions, alliances or joint ventures, Rocket’s ability to obtain and enforce patents to protect its product candidates, and its ability to successfully defend against unforeseen third-party infringement claims, as well as those risks more fully discussed in the section entitled "Risk Factors" in Rocket’s Annual Report on Form 10-K for the year ended December 31, 2024, filed February 27, 2025 with the SEC and subsequent filings with the SEC including our Quarterly Reports on Form 10-Q. Accordingly, you should not place undue reliance on these forward-looking statements. All such statements speak only as of the date made, and Rocket undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise.
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3 v To develop first-in-class and best-in-class curative gene therapies for patients with devastating diseases Generosity Trust Elevate Values Mission Curiosity ABOUT ROCKET PHARMACEUTICALS Vision: Seeking Gene Therapy Cures
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4 Multi-platform, first-and-best in-class approach to treating complex and life- threatening genetic disorders ???? Late-stage science and innovation Strong capabilities and financials Collaboration and expertise Promising clinical data designed to facilitate US and European registration and launch with potential for expansion into Asian markets and beyond First company with safety and efficacy data for gene therapies targeting the heart US-based in-house facility dedicated to AAV cGMP manufacturing ~100,000 sq ft Well capitalized to develop full pipeline of assets with approximately $222.8M1 in cash and cash equivalents; sufficient to fund operations into the second quarter of 2027 Leadership team with proven track record of US and ex-US drug approvals and launches 20+ World-class scientific experts, commercial acumen and partners learning from and closely collaborating with patient communities, HCPs and payors A Fully Integrated Gene Therapy Company ABOUT ROCKET PHARMACEUTICALS 1Cash balance as of September 30, 2025.
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5 On-target MOA; clear endpoints Sizeable market to maximize patient impact First-, best- and/or only-in- class Criteria used to select programs Strong Science, Carefully-selected Assets and Smart Execution ABOUT ROCKET PHARMACEUTICALS AAV, adeno-associated virus; ACM, Arrhythmogenic Cardiomyopathy; ATMP, advanced therapy medicinal product; BAG3, BCL2-associated athanogene 3 DCM, Dilated Cardiomyopathy; LV, lentiviral vector; MOA, mechanism of action; PKP2, plakophilin 2; PRIME, Priority Medicines; RMAT, regenerative medicine advanced therapy. Wave 2 programs DISCOVERY PRECLINICAL PHASE 1 PHASE 2 (Pivotal) Submission and Approval DESIGNATIONS Undisclosed Candidates THERAPEUTIC AREA AAV RP-A501 Danon disease AAV RP-A701 BAG3-DCM AAV RP-A601 PKP2-ACM CARDIOVASCULAR RMAT, ATMP, Fast Track, Orphan Drug (US), Rare Pediatric, PRIME RMAT, Fast Track, Orphan Drug (US/EU) RMAT, Fast Track, Orphan Drug (US/EU), PRIME LV RP-L102 Fanconi Anemia LV RP-L301 Pyruvate Kinase Deficiency HEMATOLOGY* RMAT, ATMP, Fast Track, Rare Pediatric, Orphan Drug (US/EU), PRIME RMAT, ATMP, Fast Track, Rare Pediatric, Orphan Drug (US/EU), PRIME LV KRESLADITM(RP-L201; marnetegragene autotemcel; marne cel) Severe Leukocyte Adhesion Deficiency-I *In its LV portfolio, Rocket is prioritizing KRESLADI and seeking external partnership opportunities for the RP-L102 and RP-L301 programs. Fast Track PDUFA Date: March 28, 2026
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6 IN VIVO platform EX VIVO platform RP-A501: Danon disease RP-A601: PKP2-ACM RP-A701: BAG3-DCM RP-L201: Leukocyte Adhesion Deficiency-I RP-L102: Fanconi Anemia RP-L301: Pyruvate Kinase Deficiency Laboratory- produced AAV Direct intravenous injection Therapeutic AAV Remove cells and isolate patient HSCs Infusion of modified HSCs Therapeutic LV Laboratory- produced LV Gene-modified HSCs All Rocket therapies transfer full (non-truncated) coding sequence to target tissue ABOUT ROCKET PHARMACEUTICALS Rocket Offers Multi-platform Gene Therapy Expertise AAV, adeno-associated virus; BAG3-DCM: BCL2-associated athanogene 3 Dilated Cardiomyopathy; HSCs, hematopoietic stem cells; LV, lentiviral vector; DCM, PKP2-ACM, Plakophilin 2 related Arrhythmogenic Cardiomyopathy
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7 Well-Positioned as the Leader in Cardiovascular Gene Therapies ABOUT ROCKET PHARMACEUTICALS The average heart transplant cost in the US is ~$1.7 million1 • First company with multi-year efficacy & safety data in cardiac gene therapy • Proprietary AAV manufacturing • Experience from treatment of >15 cardiac patients informs late-stage and future AAV programs • Clinical programs focus on the major phenotypes in inherited cardiomyopathies (HCM, ACM, DCM), representing a market opportunity with a large unmet need with a multi-billion-dollar commercial potential • High unmet medical need, current standard of care focuses on symptom palliation and does not address root cause • One-time IV therapy with the potential to modify disease trajectory and eliminate the need for transplant • Clear, well-established biomarkers with opportunities for accelerated approval Why Cardiomyopathy? Rocket’s Edge: Market Potential: Our three clinical programs account for >100,000 patients in the US and EU CAGR, compound annual growth rate. 1. Global Market Insights. Accessed July 2025. https://www.gminsights.com/industry-analysis/rare-disease-treatment-market Ventricular arrhythmias, Impaired heart function Dilated Cardiomyopathy Arrhythmogenic Cardiomyopathy Hypertrophic Cardiomyopathy Impaired heart function; Enlargement of heart chamber Thickening of heart wall; increased risk of arrhythmias Conventional Structure and Function AAV, adeno-associated virus; ACM, Arrhythmogenic Cardiomyopathy; DCM, Dilated Cardiomyopathy; HCM, Hypertrophic Cardiomyopathy 1. Milliman Research Report. Accessed May 2025. https://www.milliman.com/en/insight/2020-us-organ-and-tissue-transplants.
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8 Our Commitment to the Rare Disease Community Investigational Gene Therapies Natural History Studies Annual Rare Disease Day & Heart Walk ICD-10 Code Creation Allies and Partners in Patient Advocacy Market Research & Epidemiology Studies Global Focus Raising Awareness Inclusion of Patient Perspectives Mission: GENOME No-Cost Genetic Counseling and Testing ABOUT ROCKET PHARMACEUTICALS
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9 • Total Lab Space: ~30,000 sq. ft. dedicated to R&D, process and analytical development, MS&T, and QC. • GMP Manufacturing Space: ~11,000 sq. ft. for multi-product clinical manufacturing with 2X expansion capability. • Manufacturing Flexibility: From small-scale to toxicology-scale material with streamlined tech transfer to IND in <15 months. • Supply Chain Resilience: Dual-source strategy for critical materials ensuring uninterrupted supply. • Fully GMP-compliant warehouse: Enables end-to-end material control and traceability through NetSuite. • Sustainability Focus: Circular practices emphasizing reuse, in-house builds, and recycling, to enhance efficiency. Enables rapid, robust and cost-efficient internal development capability for new and existing programs in addition to full-scale commercial manufacturing facility in Cranbury, NJ ~100,000 ft2 Our R&D and Manufacturing Capabilities IND, Investigational new drug; MS&T, manufacturing, science and technology; QC, quality control; R&D, research and development. ABOUT ROCKET PHARMACEUTICALS
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10 Standard of care: • Heart transplant Limitations: • Considerable morbidity and mortality • Only ~20% of patients receive HTx2 • Not curative of extracardiac disease Therapeutic Challenges • X-linked, dominant, monogenic disease • Loss-of-function mutations in LAMP2 Disease Etiology Impaired autophagy • Prominent autophagic vacuoles • Myocardial disarray Clinical Manifestations Market Opportunity1 – US and EU Prevalence of 15,000 to 30,000 individuals Annual incidence of 800 to 1,200 individuals Severe cardiomyopathy2,3 • Severe left ventricular hypertrophy and life-threatening arrythmias • High rate of morbidity due to heart failure, with early death or HTx • Males: Aggressive disease course, median overall survival: 19 years • Females: Delayed median presentation (~20 years later) due to additional X chromosome Other clinical manifestations • Skeletal myopathy • CNS manifestations • Ophthalmologic manifestations RP-A501 for Danon Disease CNS, central nervous system; LAMP-2B, lysosome-associated membrane protein 2B; HTx, heart transplant. 1. Rocket Pharmaceuticals data on file. 2. Boucek D, Jirikowic J, Taylor M. Natural history of Danon disease. Genet Med. 2011;13(6):563-568. 3. Brambatti M, Caspi O, Maolo A, et al. Danon disease: Gender differences in presentation and outcomes. Int J Cardiol. 2019;286:92-98. RP-A501: Danon Disease
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11 Danon Disease – Epidemiology and Market Opportunity 1. Maron MS, et al. Circulation. 2018;138(15):1522-1534.; 2. Massera D, et al. Int J Cardiol. 2023;382:64-67. 3. Taylor M, et al. (2025, October 17). A Hypertrophic Cardiomyopathy-Based Model Estimate of the Prevalence of Danon Disease in the United States. [Poster abstract]. American Society of Human Genetics 2025 Annual Meeting, Boston, MA, United States. Hypertrophic Cardiomyopathy(HCM) • Anchor Population: US HCM Prevalence: 700,000 patients1,2 • Age-Adjustment: Age distribution of prevalent HCM patients likely older relative to DD patients • Weighted, Age-Adjusted Average LAMP2 Prevalence Rate: 1.85% of HCM patients consistently identified with LAMP2 mutations in multiple studies with >1,000 subjects evaluated3 Non-HCM Presenting Danon disease • Not all DD patients will present with HCM. Reliance on a model based solely on HCM underestimates the true disease burden, particularly in women and in patients presenting with other cardiac features. • Non-HCM diagnosis Upregulation: A multiplier is applied to account for male and female DD patients without an HCM diagnosis code3. • ~30% of DD males • ~50% of DD females RP-A501: Danon Disease Est. US DD Population: ~12,000 patients ↓ Max age cap (≤ 75 years old) ↓ LAMP2 Prevalence Rate (1.85%) ↑ Upregulation for broader clinical presentation
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12 Phase 2 Trial Design – Pivotal, global, single-arm, open label study of RP-A501 RP-A501: Danon Disease FDA, U.S. Food and Drug Administration; hsTnI, high-sensitivity troponin I; LAMP2, lysosome-associated membrane protein 2; LV, left ventricular; LVMI, left ventricular mass Index; IM, immunomodulatory; NYHA, New York Heart Association ClinicalTrials.gov Identifier NCT06092034. CONCURRENT NATURAL HISTORY STUDY Cohort 1: Adult/Adolescent (n=1) 6.7 x 1013 GC/kg of RP-A501 IM regimen: Rituximab + Steroid + Sirolimus Key eligibility criteria: Males age ≥8 years, LAMP2 mutation, NYHA II-III, evidence of LV hypertrophy, elevated hsTnI Co-Primary Endpoint: To support accelerated approval, co-primary endpoint consisting of improvements in LAMP2 protein expression (≥ Grade 1) and reductions in Left Ventricular Mass (LVMI; ≥10% ↓) at 12- month post-infusion. Current Status: Preparations for Cohort 4 dosing is ongoing; treatment anticipated in the first half of 2026. Cohort 2: Pediatric (n=3)+ 6.7 x 1013 GC/kg of RP-A501 IM regimen: Rituximab + Steroid + Sirolimus +Including a 90-day Pediatric Safety Run-in (n=2) Cohort 4: Pediatric and Adult/Adolescent 3.8 x 1013 GC/kg of RP-A501 IM regimen: Rituximab + Steroid + Sirolimus Cohort 3: Adult/Adolescent and Pediatric with C3 inhibitor (n=2) 6.7 x 1013 GC/kg of RP-A501 IM regimen: Rituximab + Steroid + Sirolimus + C3 inhibitor Current Stage *Staggered dosing of initial 3 patients * * * Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Next Steps: Following the treatment of three patients at 3.8x1013 GC/kg, we will align with the FDA regarding the path forward for completion of the Phase 2 pivotal study.
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13 • Pivotal, global, multicenter, single- arm, open-label Phase 2 clinical study is ongoing. • The study utilizes commercially representative RP-A501 material manufactured at our facility in Cranbury, NJ. • Phase 1 study of RP-A501 demonstrated durable protein expression, stabilization of cardiac function through 5-years post- infusion and was generally well- tolerated. • All six evaluable Phase 1 patients are alive and transplant-free. PHASE I SAFETY & EFFICACY • Treatment of Cohort 4. NEXT STEPSPIVOTAL PHASE 2 TRIAL REGULATORY DESIGNATIONS: • RMAT and PRIME • Orphan Drug designation in the US • Rare Pediatric Disease designation • Fast Track (US), ATMP Pivotal Phase 2 Trial Ongoing Development Plan ATMP, Advance Therapy Medicinal Products; PRIME, Priority Medicines; PRV, priority review voucher; RMAT, Regenerative Medicine Advanced Therapy; RP-A501: Danon Disease
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14 RP-A501 Phase I Study: Sustained LAMP2 Expression in Cardiomyocytes Durable myocardial LAMP2 protein expression seen in all patients Data up to month 36 timepoint adapted from Greenberg B., et al. N Engl J Med. 2025;392(10):972-983; Month 60 data for patient 1001 referenced from Data on file. *Patient 1001 demonstrated Grade 0 LAMP2 protein IHC staining at the 30- and 36- month assessments, however, patient 1001’s LAMP2B vector RNA and DNA (VCN) levels have persisted through 36 months of follow-up. ¶Grading of LAMP2 protein expression by IHC was done by a board-certified pathologist in a blinded fashion. The semi-quantitative grading reflects the extent of LAMP2 protein expressing cardiomyocytes in the entirety of biopsy sample according to the scale. Cohort Patient BL M6 M12 M18 M24 M30 M36 M60 6.7 × 1013 GC/kg Adult/adolescent 1001 0 NP NP 0* 0* 1002 0 NP 1005 0 NP NP 1.1 × 1014 GC/kg Adult/adolescent 1006 0 NP 6.7 × 1013 GC/kg Pediatric 1008 0 NP 1009 0 NP Myocardial LAMP2 Protein Expression † †Reflects patient 1005 9M visit biopsy as 12M biopsy not performed ‡Preliminary assessment of biopsy from 1001 Y5 visit with updated IHC assay Grade 0 = no staining NP = not performed = Grade 1 (≤25%) = Grade 2 (26%–50%) = Grade 3 (51%–74%) = Grade 4 (≥75%) Legend: IHC Staining Grade¶ (% Positive Cardiomyocytes) Pre-infusion Visit 0 Post-infusion Visit 1 Post-infusion Visit 2 Post-infusion Visit 3 10081009 6.7 × 1013 GC/kg Pediatric, N=2 10021005 6.7 × 1013 GC/kg Adult/adolescent, N=3 100 µm M6 M6 M12 M12 M24 M24 M12 M9 M24 M24 M36 M36 Representative LAMP2 IHC Images 100 µm ‡ RP-A501: Danon Disease
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15 RP-A501 Phase 1 Study: Sustained Improvements in LV Mass Index -16% -14% -10% -11% -32% -15% 1001 1002 1005 1006 1008 1009 -27% -48% -11% -7% -38% -13% 1001 1002 1005 1006 1008 1009 Data published in Greenberg B., et al. N Engl J Med. 2025;392(10):972-983 [supplementary appendix]; Data cut-off: April 19, 2024. * Where possible, cardiac MRI assessments shown (patients 1001, 1006, and 1009); otherwise, echocardiogram data presented. All assessments were conducted by a single reviewer blinded to both patient and timepoint, except for Patient 1001 cardiac MRI data, which includes reads from multiple reviewers (note, these data not included in NEJM publication). Patient 1001 most recent visit with MRI assessment was at 48m † Utilized 9m or 18 m data when 12m assessment was not done. LVMI, left ventricular mass index; MRI, magnetic resonance imaging; m, month(s). LVMI % Change: Baseline to 12m† All patients showed ≥10% LVMI decrease at ~12m; improved or sustained at most recent visit LVMI % Change: Baseline to Most Recent Visit* *** * * * M12 M18† M9† M12 M12 M12 M48 M54 M42 M36 M24 M24 -70% -50% -30% -10% 10% 30% 1001 1002 1005 1006 1008 1009 LVMI % Change from Baseline ** * RP-A501: Danon Disease
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16 Primary Endpoint Reasonably Likely to Predict Clinical Benefit Justification for use of LAMP2 protein expression and LV Mass • Mutation of LAMP2 is root cause of Danon disease • Epidemiologic support: even modest levels of LAMP2 confer a 2-decade survival advantage in female patients • RP-A501 delivers full coding sequence of WT LAMP2 gene • Pre-clinical LAMP2 restoration conferred histologic, functional and survival benefits in LAMP2 knock-out model1 • Phase 1: LAMP2 expression associated with decreased vacuolar area, improved myofibrillar disarray, clinical improvement WT Full Length LAMP2 Protein Expression Left Ventricular Mass • Severe left ventricular hypertrophy (LVH) is the most common manifestation • Severity of the cardiomyopathy in Danon disease is the major prognostic factor • Retrospective natural history shows year-over-year increases in LV mass in Danon disease patients • Phase 1: Consistent and significant reductions in LV mass as early as 6 months by echocardiography and cardiac MRI Primary Endpoint Will Be Interpreted in a Clinical Context: • All components are measurable and unlikely to improve in the absence of a true treatment effect • Primary endpoint will be assessed in the context of biomarkers, symptoms, QoL, clinical events derived from secondary endpoints and concurrent natural history study • Phase 1 trial: LAMP2 expression and LV Mass improvements seen as early as 6 months in pediatric subjects with updated immunomodulation regimen LAMP2, lysosome-associated membrane protein 2; LV, left ventricle; MRI, magnetic resonance imaging; QOL, quality of life; WT, wild type . 1.Manso 2020. Sci Transl Med RP-A501: Danon Disease
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17 RP-A501 Phase I Study: Benefit Observed Across All Key Parameters Early LAMP2, BNP , TnI changes associated with sustained clinical improvement and guided Phase 2 endpoint selection Data published and used with permission from Greenberg B., et al. N Engl J Med. 2025;392(10):972-983; Data cut-off: April 19, 2024. BL, Baseline; BNP , Brain Natriuretic Peptide; cTnI, cardiac troponin I; ICD, Implantable Cardioverter Defibrillator; IVSd, Intraventricular Septum in diastole; KCCQ, Kansas City Cardiomyopathy Questionnaire; NT- Pro-BNP , N-terminal pro–B-type natriuretic peptide; NYHA, New York Heart Association; LV, Left Ventricle; LVEF, Left Ventricular Ejection Fraction; LVMI, Left Ventricular Mass Index, LVPWd, Left Ventricular Posterior Wall in diastole, RV, (Most) Recent Visit. Improved Stabilized Worsened Cohort Patient Age at Most RV (y) Most Recent Visit (mo) LVEF BL to RV (%) Δ LVMI,* BL to RV (g/m2.7) Δ IVSd, BL to RV (mm) Δ LVPWd, BL to RV (mm) Δ NT-proBNP, BL to RV (ng/L) Δ cTnI,† BL to RV (ng/mL) Δ NYHA Class Δ KCCQ-12 OS, BL → RV 1:Low Dose Adult/ Adolescent 1001 22.3 54 57 to 64 -33%, 85 to 56.9 -6%, 19.8 to 18.6 -20%, 18.8 to 15 -17%, 336 to 279 -99% 0.6 to 0.01 II to I +52, 44 to 96 1002 24.9 54 55 to 66 -48%, 260.2 to 135.3 -52%, 60.1 to 28.6 -49%, 39.1 to 19.8 -93%, 5119 to 351 -96%, 1.46 to 0.06 II to I +27, 64 to 91 1005 21.8 42 65 to 59 -11%, 98.2 to 87.3 -10%, 30.9 to 27.8 -27%, 32.1 to 23.4 +16%, 841 to 975 -33%, 0.28 to 0.19 II to I +7, 77 to 84 2:High Dose Adult/ Adolescent 1006 23.9 36 62 to 51 -7%, 68.6 to 63.6 +5%, 18.0 to 19.0 -27%, 24.0 to 17.4 -65%, 720 to 249 -39%, 0.47 to 0.29 II to I +9, 79 to 89 3:Low Dose Pediatric 1008 14.4 24 74 to 78 -38%, 141.5 to 87.8 -19%, 42.4 to 34.2 +1%, 22.8 to 23.1 -78%, 1629‡ to 360‡ -85%, 1.78 to 0.27 II to I +27, 50 to 77 1009 13.7 24 77 to 77 -13%, 82.0 to 71.2 +12%, 18.5 to 20.8 -3%, 14.9 to 14.4 -48%, 1912 to 998 -82%, 1.08 to 0.20 II to I +30, 52 to 82 * Centrally evaluated (blinded) MRI data were utilized for LVMI when available. All other measurements of cardiac structure a nd function reflect centrally evaluated (blinded) echocardiogram data. † Central laboratory assessment of cTnI were performed on cryopreserved and non -cryopreserved samples. Values for cTnI from high-sensitivity and earlier tests. high-sensitivity and earlier assay are expressed in ng/mL. RP-A501: Danon Disease
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18 RP-A501 Phase 1 Study: Reduction in Troponins and HF Symptoms Troponin Levels a Key Secondary Endpoint That Correlates with Reductions in Measures of Cardiac Injury and HF Symptoms Data published in Greenberg B., et al. N Engl J Med. 2025;392(10):972-983 [supplementary appendix]; Data cut-off: April 19, 2024 aVisits not conducted, and results pending or unavailable at various timepoints; data shown are cTnI levels performed on high-sensitivity and older assays. Values from both assays are expressed in nanograms per milliliter for consistency. B Representative Troponin Upper Limit of Normal: 0.04 ng/mL. cTnI, cardiac troponin I; HF, heart failure; KCCQ-OS, Kansas City Cardiomyopathy Questionnaire – Overall Score; M, month(s); NYHA, New York Heart Association; ULN, upper limit of normal. • Troponins significantly elevated in all subjects at baseline; marked decreases and/or stabilization sustained 2-4.5 years post treatment. • Associated with clinical improvement to NYHA Class I in all patients (Class I = no clinical symptoms of HF) • Patient reported outcomes (KCCQ) further support reduction in HF symptoms and improved quality of life out to 4.5 yrs Patient ID NYHA Class Baseline NYHA Class* Most Recent Follow-up Δ KCCQ-12 OS, BL → RV Time of Follow-up 1001 II I +52 4.5 yrs 1002 II I +27 4.5 yrs 1005 II I +7 3.5 yrs 1006 II I +9 3 yrs 1008 II I +27 2 yrs 1009 II I +30 2 yrs Corresponding Improvement in NYHA class and KCCQ-OS after Treatment with RP-A501 Sustained Reduction in Cardiac Troponin-I Levelsa after Treatment with RP-A501 0.00 0.20 0.40 0.60 0.80 1.00 1.20 1.40 1.60 1.80 2.00 Baseline M12 M18 M24 M30 M36 M42 M48 1001 1002 1005 1006 1008 1009 ULNb RP-A501: Danon Disease
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19 RP-A501 Phase I Study: Decreased Cardiomyocyte Vacuolization Enhanced autophagy leads to improved myocardial ultrastructure and clinical phenotype Representative Images from the Endomyocardial Biopsy of Patient 1008 Data published in Greenberg B., et al. N Engl J Med. 2025;392(10):972-983 [supplementary appendix]; Data cut-off: April 19, 2024 RP-A501: Danon Disease
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20 Fabry Disease (Agalsidase alfa) 1 Data Cutoff April 9, 2024; Mean change from baseline includes only patients treated with Low Dose (6.7x10^13 GC/kg) and calculated as follows: M6 = 1001,1008,1009 (no 6M data for 1002,1005); 1Y = 1001,1008,1009 12M data and 1002,1005 18M data (no data from 1002,1005 12M visits); 2Y = 1001,1002,1005,1008,1009 24M data; 3Y = 1001,1002,1005 36M data, 4Y = 1001,1002 48M data. * Where possible, cardiac MRI assessments shown (patients 1001, 1006, and 1009); otherwise, echocardiogram data used.. All assessments were conducted by a single reviewer blinded to both patient and timepoint, except for Patient 1001 cardiac MRI data, which includes reads from multiple reviewers. 2 Reflects estimated LV Mass increase over 12-18M for DD patients based on retrospective natural history data-set. Data for comparable therapies from the following publications: Hughes et al. Heart 2008; Rettl et al. EHJ CV Imaging 2022; Solomon et al. Circulation 2019.; Saberi et al. Circulation 2021. LV Mass @6M LV Mass @18M LVMI @7M Amyloid Cardiomyopathy (Patirisan) HCM (Mavacamten) Danon Disease (RP-A501 Phase 1 Study – Low Dose Adult and Pediatric Cohorts) @6M Placebo / Untreated TreatedEstimate from retrospective NxHx Data @4Y Clinical Correlation: • Improvements in LVM out to 36M correlated with HF symptoms (NYHA, CCS); drug approved in EU Clinical Correlation: • Drug approved based on improved CV outcomes @30M • Significant improvements in 6MWD & NT-proBNP Clinical Correlation: • ↑ exercise tolerance at 30wks • NYHA Class ↓ by 1 in 76% treated patients at 120wks Clinical Correlation: • NYHA Class improvement, KCCQ ↑, improvement or stabilization in hsTnI and natriuretic peptides all to most recent timepoint (24-56M) Est. LVM Increase per NxHx2 LV Mass / LV Mass Index (LVMI) Improvements with Low Dose RP-A501 Comparable to Other Recently Approved Therapies for Cardiomyopathy @1Y @2Y @3Y Mean LV Mass Index Change from Baseline1 8.8% -4.1% <1% -5.6% -1.7% -17% 8% -17% -19% -23% -30% -47% RP-A501: Danon Disease
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21 -50% -40% -30% -20% -10% 0% 10% 20% Baseline 6M 9-18M 2Y 3Y 4Y LV Mass / LV Mass Index (LVMI) Improvements with RP-A501 Comparable to Other Recently Approved Therapies for Cardiomyopathy (12M); -19.1% DD RP-A501 Low Dose Tx1 Fabry – Agalsidase Alfa Untreated (6M); +9% Amyloidosis – Tafamidis Treated (9M); -3.6% HCM - Mavacamten Untreated (7M); -1.7% Amyloidosis – Patisiran Untreated (18M); +1% Amyloidosis – Tafamidis Untreated (9M); +8.1% Amyloidosis – Patisiran Treated (18M); -5.6% HCM - Mavacamten Treated (7M); -17% DD UnTx @12M (Estimated based on Retro NxHx2); +8% • Data from Phase 1 study shows RP-A501 is potentially transformative for cardiac structure improvements and remodeling • On par with recently approved therapies in other CV indications at similar timepoints (across different disease etiologies and drug MOA’s) • Sustained improvements seen with longer follow-up LV Mass / LVMI Change from Baseline in Treated vs Untreated Patients: RP-A501 Low-Dose Adult and Pediatric Patients1 and Recently Approved CV Therapies 1 Data Cutoff April 9, 2024; Mean change from baseline includes only patients treated with Low Dose (6.7x10 ^13 GC/kg) and calculated as follows: M6 = 1001,1008,1009 (no 6M data for 1002,1005); 1Y = 1001, 1008,1009 12M data and 1002,1005 18M data (no data from 1002,1005 12M visits); 2Y = 1001,1002,1005,1008,1009 24M data; 3Y = 1001,1002,1005 36M data, 4Y = 1001,1002 48M data. * Where possible, cardiac MRI assessments shown (patients 1001, 1006, and 1009); otherwise, echocardiogram data used. All assessments were conducted by a single reviewer blinded to both patient and timepoint, except f or Patient 1001 cardiac MRI data, which includes reads from multiple reviewers. 2 Reflects estimated LV Mass increase over 12 -18M for DD patients based on retrospective natural history data -set. Data for comparable therapies from the following publications: Hughes et al. Heart 2008; Rettl et al. EHJ CV Imaging 2022; Solomon et al. Circulation 2019.; Saberi et al. Circulation 2021. (6M); -17.2% (2Y); -23.5% (3Y); -29.9% (4Y); -47.2% Fabry – Agalsidase Alfa Treated (6M); -4% RP-A501: Danon Disease
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22 Insights from Danon Disease Patients Treated on the Phase 1 Trial He went to overnight summer camp on his own for the first time and is no longer out of breath walking up stairs. (Patient 1008) Prior to therapy, he would say "my wish is not to die young." After gene therapy, we see him smile more because he was able to hold down a steady part-time job and can live independently in an apartment of his own. He is living a life he didn't think would be possible. (Patient 1006) He is now able to exercise on a more regular basis. After treatment, he was able to participate in an organized walk with his father completing most of the 10K course. (Patient 1009) He can walk upstairs without being short of breath or having to stop half-way. He doesn’t have chest pain or fast heart rates like he used to. Another amazing thing we have seen is about 4 months after his therapy trial he started working and stopped using his motorized scooter altogether. (Patient 1005) RP-A501: Danon Disease
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23 Standard of Care • Beta-blockers, anti-arrhythmic agents, ICD, and ablation. Limitations • Available treatments do not modify disease progression; no curative therapeutic options • ICD firings are lifesaving but highly traumatic events Therapeutic Challenges • Autosomal dominant mutations in PKP2 gene, which encodes for Plakophilin-2, a component of the desmosome localized to cardiac intercalated discs Disease Etiology Clinical Manifestations RP-A601 for PKP2-Arrhythmogenic Cardiomyopathy (ACM) In one study population of 439 ARVD/ARVC patients (median follow up, 7 years): 4 • >70% experienced sustained ventricular arrhythmias VAs • >80% received ICD placement • ~11% of patients experienced sudden cardiac death (SCD) or resuscitated SCD Figures used with permission from Tadros HJ, et al. Appl Clin Genet. 2023. and Asimaki A, et al. N Engl J Med. 2009. ARVC, arrhythmogenic right ventricular cardiomyopathy; ARVD, arrhythmogenic right ventricular dysplasia;ECG, electrocardiogram; EPS, electrophysiologic study; ICD, implantable cardioverter defibrillator; LV, left ventricle; RV, right ventricular; SCD, sudden cardiac death; TWI, T-wave inversion; VT, ventricular tachycardia. 1.Rocket Pharmaceuticals data on file; 2. James CA, et al. J Am Coll Cardiol. 2013. 3. Bhonsale et al. Eur Heart J. 2015; 4. Groeneweg et al. Circ Cardiovasc Genet. 2015. RP-A601: PKP2-ACM Market Opportunity1 – US and EU Prevalence of 50,000 individuals Concealed Phase Overt Phase End-stage Disease Normal imaging Electrical manifestations Ventricular dilation, arrhythmia, SCD Normal PKP2-ACM Cadherin-2 PKP2 Susceptibility2 • Frequent and/or endurance exercise are associated with increased likelihood of ACM diagnosis and severity; patients are often advised to avoid strenuous activity Associated Risks3 • Mean age at presentation: 35y (±18) • Disease progression may lead to heart failure, premature death, or transplant
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24 2,572 ACM patients assessed from 13 publications an aggregated mean of 32.9% had PKP2 mutations3 Utilizing the conservative ACM prevalence (1:5000) and the 32.9% PKP2 mutation frequency in ACM PKP2-ACM Prevalence in the US and EU 1:1000 to 1:5000 1,2 ACM prevalence 32.9% PKP2 variants ~50,000 ACM-PKP2 US & EU Prevalence 1. Peters S, Trümmel M, Meyners W. Prevalence of right ventricular dysplasia-cardiomyopathy in a non-referral hospital. Int J Cardiol. 2004;97(3):499-501. 2. McKenna WJ, Judge DP. Epidemiology of the inherited cardiomyopathies. Nat Rev Cardiol. 2021;18(1):22-36. 3. Rocket Pharmaceuticals data on file. RP-A601: PKP2-ACM
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25 Phase 1 Trial Design of RP-A601 in Adult Patients with PKP2-ACM First-in-human, multi-center, open-label, dose escalation trial PRIMARY ENDPOINT: SAFETY • Incidence of TEAEs and SAEs • Identification of dose limiting toxicities INCLUSION CRITERIA • Male or female ≥18 years • Clinical diagnosis of ACM as defined by the 2010 revised Task Force Criteria • Pathogenic or likely pathogenic truncating variant in PKP2 • Anti-AAVrh.74 capsid neutralizing antibody assay ≤1:40 • History of ICD implantation ≥6 months prior to enrollment EXCLUSION CRITERIA • Cardiomyopathy related to a genetic etiology other than PKP2 truncating variant • Previous participation in a study of gene transfer or gene editing • Severe right ventricular dysfunction • Left ventricular ejection fraction by echocardiogram ≤50% • New York Heart Association Class IV heart failure Natural history studies planned to provide context for the Phase 1 trial and additional information on disease progression ACM, arrhythmogenic cardiomyopathy; GC, genome copies; ICD, implantable cardioverter-defibrillator; IV, intravenous; SAE, serious adverse event; TEAE, treatment emergent event. Phase 1 Trial of RP-A601 in Adult Patients with PKP20ACM (NCT05885412) PKP2-ACM Natural History Study (NCT06644742) RP-A601: PKP2-ACM SECONDARY & EXPLORATORY ENDPOINTS: EFFICACY • Change in PKP2 protein expression • Change in frequency of clinical markers of life- threatening ventricular arrhythmias • Cardiac biomarkers Starting Dose (RP-A601): 8 x 1013 GC/kg (IV) Month 3 Month 12 Long-Term Follow-Up Yearly Safety Monitoring Month 24Month 6 Month 9 Safety and Efficacy Assessments Month 0 Month 18 ≥60 Months
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26 Summary of Initial Results From Ongoing Phase I Trial and Path Forward Cohort 1 Patients (n=3) with PKP2-ACM Treated with RP-A601 Demonstrated: • RP-A601 was generally well-tolerated with no dose-limiting toxicities observed ► No TMA or ventricular arrhythmias were observed • All 3 patients demonstrated cardiac transduction with localized myocardial protein expression (PKP2, Desmocollin- 2, Cadherin-2) that was maintained or increased up to 12-months post-infusion • Preliminary indications of improvement or stabilization observed in arrhythmia burden, heart function, and quality of life with up to 12-months of follow-up ► Decreased/stabilized ventricular ectopy (PVC, NSVT) on rhythm monitoring in all patients ► Decreased/stabilized T-wave inversions on ECG in all patients ► Improved/stabilized RV function ► Improved quality-of-life and NYHA Class in patients followed beyond 6 month With no further dose escalation plans, Rocket is engaging with FDA on a potential pivotal trial design to evaluate the efficacy and safety of RP-A601 ECG, electrocardiogram; FDA, U.S. Food and Drug Administration; NSVT, non-sustained ventricular tachycardia; NYHA, New York Heart Association Functional classification; PVC, premature ventricular contractions; RV, right ventricular; TMA, thrombotic microangiopathy RP-A601: PKP2-ACM
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27 Preliminary Indications of Improvement or Stabilization Observed in Clinical Markers of Arrhythmia Burden, Heart Function and QoL Patient ID Age at Enrollment (y) Most Recent Visit (MRV, mo) RV Systolic Function (ECHO) BL→ MRV KCCQ-12 Score BL→ MRV (% change) NYHA Class BL*→ MRV PVCs per 24h BL → MRV (% change) NSVTs per 24h BL→ MRV T-wave inversions (precordial and inferior ECG) 1003 55 12 Normal → Normal† 39.6 → 74.0 (+87%) II → I 117** → 43 (-63%) 0 → 0 0 → 0 1011 58 9 Mild - moderate reduced → Normal 54.2 → 95.3 (+76%) II → I 2974 → 2713 (-9%) 0 → 0 4 → 4 1010 36 6 Normal → Normal 59.4 → 59.4 (0%) II → II 2650** → 1057 (-60%) 5** → 0 6 → 2 BL, baseline; h, hours; KCCQ, Kansas City Cardiomyopathy Questionnaire; mo, months; MRV, most recent visit; NSVT, non-sustained ventricular tachycardia; NYHA, New York Heart Association; PVC, premature ventricular contractions; QoL, quality of life; RVEF, right ventricular ejection fraction; y, years. Data cutoff April 2025. *As assessed on Day-14 pre-infusion. **Ambulatory rhythm monitoring was conducted at baseline for 48 hours. For the specified patients, data from two separate 48-hour rhythm monitoring studies were combined to produce the baseline value. Rhythm monitoring at the most recent visit was conducted for 7 days. †Stability of RVEF was corroborated by month 12 cardiac magnetic resonance (CMR) s imaging. Arrhythmia BurdenHeart Function & QoL RP-A601: PKP2-ACM
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28 Therapeutic Challenges • Autosomal dominant mutations in BAG3 gene • Loss of BAG3 leads to an accumulation of misfolded and damaged proteins, which impairs the heart’s ability to contract, leading to heart failure Disease Etiology Clinical Manifestations RP-A701 for BAG3-Dilated Cardiomyopathy (BAG3-DCM) BAG3, BCL2-associated athanogene 3; BCL2, B-cell lymphoma; DCM, dilated cardiomyopathy; ICD, implantable cardioverter defibrillator; IND, investigational new drug; LVEF, left ventricular ejection fraction; SOC, Standard of Care; 1. Domínguez et al. JACC 2018; 2. Martin et al., Circulation, 2024. 3. Hershberger et al., Nat Rev Cardiol, 2013; 4. Petretta et al., Am J Cardiol, 2011. RP-A701: BAG3-DCM Market Opportunity1,2 – US Prevalence of 30,000 individuals Standard of Care (SOC): • Medical therapies for heart failure and/or interventional therapies (ICD, cardiac resynchronization, and heart transplant) Limitations: • Available treatments do not address the underlying cause of disease and are not curative Susceptibility • 20% to 50% of DCM patients have familial DCM; up to 40% of whom have an identifiable genetic cause3,4 • 80% of patients over 40 years of age with a BAG3 mutation will present with the disease.2 • Pathogenic variants in BAG3 are estimated to cause 2.3% to 6.7% of DCM cases in the U.S., Europe, and Japan2 Associated Risks • Patients have significant limitations in activities of daily living (e.g., employment, walking, personal care) • SOC therapies demonstrate limited efficacy, with only 2.9% of BAG3-DCM patients experiencing normalization of LVEF during follow-up 2 • Heart transplantation is the only definitive therapy, but carries short- and long-term risks, including post- transplant mortality, and limited by availability
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29 ► We believe that a gene therapy approach is best positioned to restore the broad biological functions of BAG3 in the heart ► Phase 1 trial start-up activities are currently underway for RP-A701, and we are working towards treating the first patient Cardiovascular Health is Dependent on Functional BAG3 Protein 4 Cardiac contractility Enhances contractility by linking the β-adrenergic receptor and L-type Ca2+ channel Provides support for the sarcomere by linking actin myofibrils with the Z-disc Structural support Facilitates autophagy as aco- chaperone with heat shock proteins, recycling misfolded proteins Protein quality control Inhibits apoptosis (programmed cell death) through binding of BCL2 Anti-apoptosis BAG3, BCL2-associated athanogene 3; BCL2, B-cell lymphoma 2. Knezevic T et al. JACC Basic Transl Sci. 2016.; Myers et al. JAMA Cardiol. 2018. BAG3 regulates critical functions in cardiomyocytes RP-A701: BAG3-DCM
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30 Phase 1 Trial Design of RP-A701 in Adult Patients with BAG3-DCM First-in-human, open-label, dose escalation trial PRIMARY ENDPOINT: SAFETY • Incidence of TEAEs • Incidence of SAEs • Identification of dose limiting toxicities INCLUSION CRITERIA • Individuals between 18-65 years with a clinical diagnosis of DCM • Pathogenic or likely pathogenic variant in BAG3 • History of ICD implantation ≥3 months prior to enrollment • NYHA Class II or III HF symptoms with stable HF therapeutic guideline-directed medical regimen for ≥ 30 days enrollment EXCLUSION CRITERIA • Cardiomyopathy related to an etiology other than BAG3 mutations • Previous participation in a study of gene transfer or gene editing • I.V. inotropic, vasodilator, or diuretic therapy ≤ 30 days prior to enrollment • Severe right ventricular dysfunction • Left ventricular ejection fraction by echocardiogram <25% BAG3-DCM, BAG3 related Dilated Cardiomyopathy; HF, Heart Failure; ICD, implantable cardioverter-defibrillator; IV, intravenous; NYHA, New York Heart Association; SAE, serious adverse event; TEAE, treatment emergent adverse event. Clinicaltrials.gov Identifier: NCT07137338. SECONDARY & EXPLORATORY ENDPOINTS: EFFICACY • Change in BAG3 protein expression • Change in clinical markers of cardiovascular function and heart failure • Quality of life Dose of RP-A701 (IV) Month 3 Month 12 Long-Term Follow-Up Yearly Safety Monitoring Month 24Month 6 Month 9 Safety and Efficacy Assessments Month 0 Month 18 ≥60 Months RP-A701: BAG3-DCM
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31 Patients suffer from recurrent infections; fatal in majority 2 • Severe LAD-I: Death prior to age 2 in 60% to 75% of patients, infrequent survival >5 years in absence of allogeneic HSCT • Moderate LAD-I: Death prior to age 40 in >50% of patients, extensive morbidity with recurrent infections and inflammatory lesions Clinical manifestations • ITGB2 gene mutations (21q22.3), encoding the beta-2-integrin, CD18; essential for leukocyte adhesion to endothelium • CD18 absent or reduced on neutrophils Disease etiology Standard of care: • Allogeneic HSCT Limitations: • Donor availability • Infections • Frequent GvHD • Graft failure Therapeutic challenges Market Opportunity1 – US and EU Prevalence of 800 to 1,000 individuals Annual incidence of 50 to 75 individuals RP-L201 for Severe LAD-I GvHD, graft-versus-host disease; HSCT, hematopoietic stem cell transplant; ITGB2, integrin subunit beta 2; LAD-I, leukocyte adhesion deficiency-I. 1. Rocket Pharmaceuticals data on file; 2. Almarza Novoa et al. J Allergy Clin Immunol Pract. 2018. RP-L201: LAD-I
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32 • Survival for 9/9 patients, ≥2 years age and ≥1 year post-treatment • No graft failure or GvHD • No RP-L201 related SAEs • Efficacy observed in 9/9 patients with 12 to 36 months follow-up • Efficacy is comprehensive, across all efficacy parameters including CD18 expression and survival INITIAL EFFICACY • BLA resubmission was accepted by the FDA in October 2025 • PDUFA date is March 28, 2026 • Rocket is eligible for a PRV, upon its potential approval NEXT STEPSTOP-LINE DATA READOUT PDUFA date is March 28, 2026 Development Plan ATMP, Advance Therapy Medicinal Products; BLA, Biologics License Application; FDA, U.S. Food and Drug Administration; GvHD, graft versus host disease; PRIME, Priority Medicines; PRV, priority review voucher; RMAT, Regenerative Medicine Advanced Therapy; SAEs, serious adverse events. RP-L201: LAD-I REGULATORY DESIGNATIONS: • RMAT and PRIME • Orphan Drug designation in the US and EU • Rare Pediatric Disease designation (eligible for PRV) • Fast Track (US), ATMP
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33 CD18 Expression in PB Polymorphonuclear Cells in Pivotal Trial Sustained >10% PMN CD18 expression 1 year after gene-corrected cell infusion across the entire cohort *Baseline dim or weak CD18 neutrophil expression in Patient 2 in 63.4% of cells with CD11a or CD11b neutrophil expression of less than 2% most likely indicates abnormal or unstable protein. †Baseline CD18 neutrophil expression in Patient 3 in 5.8% of cells with CD11a or CD11b neutrophil expression of less than 2% most likely indicates abnormal or unstable protein. PB, peripheral blood; PMN, polymorphonuclear neutrophil. Data cutoff July 24, 2023. Images used with permission from Booth et al. N Engl J Med. 2025. RP-L201: LAD-I
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34 Survival without allogeneic HSCT Primary outcomes • ≥1-year post–RP-L201 infusion AND • ≥2 years of age for subjects enrolled <1 year of age 100% HSCT-free survival Kaplan–Meier estimate Meaningful reduction in infection-related hospitalizations following immune reconstitution • Infections that developed beyond 90 days post-infusion were consistent with typical childhood infections frequently observed in immunocompetent (healthy) children • All patients have been able to stop prophylactic antibiotics (when permitted by institutional policy) Reduction in Hospitalizations and 100% HSCT-free Survival in Pivotal Trial * Predefined serious infections were those infections requiring hospitalization or parenteral (intravenous) antimicrobials. † Annualized event rate is calculated as the Total Number of Events / Total Time. Results are adjusted event rate per year. Pre-infusion includes all lifelong medical history prior to RP-L201 infusion. CI, confidence interval; d, day; EoS, end of study; HSCT, hematopoietic stem cell transplantation; mo, month. Data cutoff July 24, 2023. Adapted from Booth et al. N Engl J Med. 2025. †* RP-L201: LAD-I
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35 Future Therapies: Wave 2 (AAV) We continue to build our pipeline based on our core R&D strategy, identifying the “most impactful” indications for the most efficient development path. On-target MOA; clear endpoints Sizeable market to maximize patient impact First-, best- and/or only-in-class Current Clinical Pipeline Focused R&D Strategy for Sustainable Innovation AAV, adeno-associated virus; CV, cardiovascular; MOA, mechanism of action; R&D, research and development. FUTURE DIRECTIONS
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36 Expert Leadership With Proven Track Record Gaurav Shah, M.D. Chief Executive Officer Spearheaded Kymriah development at Novartis towards approval. Jonathan Schwartz, M.D. Chief Science & Gene Therapy Officer Led multiple biologics approvals. Martin Wilson, J.D. General Counsel & Chief Corporate Officer ~20 years legal, compliance and executive experience and accomplishment in life sciences. Sarbani Chaudhuri Chief Commercial & Medical Affairs Officer 20+ years of experience driving commercial growth for rare cardiac and hematology launches. EXPERIENCED MANAGEMENT TEAM Chris Stevens Chief Operating Officer 25 years of proven success in technical operations, product strategy, and leadership. Syed Rizvi, M.D. Chief Medical Officer 20+ years of experience across all stages of drug development. Meg E. Dodge, J.D., LL.M Senior Vice President, Head of External Affairs 15+ years of experience with capital markets, strategic communications, and corporate operations.
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37 THANK YOU!